Valbenazine, also known as NBI-98854, is a highly selective, vesicular monoamine transporter 2 (VMAT2) inhibitor in clinical development for the treatment of tardive dyskinesia. It is a L-valine (2R,3R,11bR)-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H-benzo(a)quinolizin-2-yl ester and has the following chemical structure according to Formula I.

Valbenazine is an inhibitor of vesicular monoamine transporter isoform 2 (VMAT2) and is being developed for the treatment of different central nervous system disorders, particularly involuntary hyperkinetic movement disorders such as drug-induced tardive dyskinesia and Tourette's syndrome. Valbenazine was approved in the U.S. for the treatment of tardive dyskinesia (TD) and is marketed under the commercial name of INGREZZA® as a ditosylate salt.
U.S. Pat. No. 8,039,627 discloses valbenazine and its pharmaceutically acceptable salts or solvates.
U.S. Pat. No. 10,065,952 discloses six crystalline forms and an amorphous form of valbenazine ditosylate.
Patent application WO 2018/067945 discloses ten crystalline forms of valbenazine ditosylate.
Patent application WO 2019/104141 discloses a crystalline form of valbenazine ditosylate.
Patent application WO 2018/153632 discloses two crystalline forms of valbenazine ditosylate.
Patent applications EP 3,473,623, WO 2018/067945, WO 2018/130345, and WO 2018/153632, disclose crystalline forms of valbenazine and valbenazine salts.
Polymorphism, the occurrence of different crystal forms, is a property of some molecules and molecular complexes. A single compound, like valbenazine, may give rise to a variety of polymorphs having distinct crystal structures and physical properties like melting point, thermal behaviors (e.g., measured by thermogravimetric analysis (“TGA”), differential scanning calorimetry (“DSC”) or dynamic vapor sorption (“DVS”)), X-ray powder diffraction (“XRPD”) pattern, infrared absorption fingerprint and Raman absorption fingerprint. One or more of these techniques may be used to distinguish different polymorphic forms of a compound.
Discovering new solid-state forms, including hydrates and solvates, of an active pharmaceutical ingredient can provide materials having desirable processing properties, such as ease of handling, ease of processing, storage stability, and ease of purification or as desirable intermediate crystal forms that facilitate conversion to other salts or polymorphic forms. New polymorphic forms and solvates of an active pharmaceutical ingredient can also provide an opportunity to improve the performance characteristics of a pharmaceutical product (dissolution profile, bioavailability, etc.). It enlarges the repertoire of materials that a formulation scientist has available for formulation optimization, for example by providing a product with different properties, e.g., a different crystal habit, higher crystallinity or polymorphic stability which may offer better processing or handling characteristics, improved dissolution profile, or improved shelf-life.
Hence, there is a need for additional solid-state forms of valbenazine ditosylate with suitable characteristics for an oral formulation.